Functional investigation suggests CNTNAP5 involvement in glaucomatous neurodegeneration obtained from a GWAS in primary angle closure glaucoma.
Primary angle closure glaucoma (PACG) affects more than 20 million people worldwide, with an increased prevalence in south-east Asia. In a prior haplotype-based Genome Wide Association Study (GWAS), we identified a novel CNTNAP5 genic region, significantly associated with PACG. In the current study,...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2024-12-01
|
| Series: | PLoS Genetics |
| Online Access: | https://doi.org/10.1371/journal.pgen.1011502 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841555610910326784 |
|---|---|
| author | Sudipta Chakraborty Jyotishman Sarma Shantanu Saha Roy Sukanya Mitra Sayani Bagchi Sankhadip Das Sreemoyee Saha Surajit Mahapatra Samsiddhi Bhattacharjee Mahua Maulik Moulinath Acharya |
| author_facet | Sudipta Chakraborty Jyotishman Sarma Shantanu Saha Roy Sukanya Mitra Sayani Bagchi Sankhadip Das Sreemoyee Saha Surajit Mahapatra Samsiddhi Bhattacharjee Mahua Maulik Moulinath Acharya |
| author_sort | Sudipta Chakraborty |
| collection | DOAJ |
| description | Primary angle closure glaucoma (PACG) affects more than 20 million people worldwide, with an increased prevalence in south-east Asia. In a prior haplotype-based Genome Wide Association Study (GWAS), we identified a novel CNTNAP5 genic region, significantly associated with PACG. In the current study, we have extended our perception of CNTNAP5 involvement in glaucomatous neurodegeneration in a zebrafish model, through investigating phenotypic consequences pertinent to retinal degeneration upon knockdown of cntnap5 by translation-blocking morpholinos. While cntnap5 knockdown was successfully validated using an antibody, immunofluorescence followed by western blot analyses in cntnap5-morphant (MO) zebrafish revealed increased expression of acetylated tubulin indicative of perturbed cytoarchitecture of retinal layers. Moreover, significant loss of Nissl substance is observed in the neuro-retinal layers of cntnap5-MO zebrafish eye, indicating neurodegeneration. Additionally, in spontaneous movement behavioural analysis, cntnap5-MO zebrafish have a significantly lower average distance traversed in light phase compared to mismatch-controls, whereas no significant difference was observed in the dark phase, corroborating with vision loss in the cntnap5-MO zebrafish. This study provides the first direct functional evidence of a putative role of CNTNAP5 in visual neurodegeneration. |
| format | Article |
| id | doaj-art-824af1cae4954b328685ed82edd651ab |
| institution | Kabale University |
| issn | 1553-7390 1553-7404 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj-art-824af1cae4954b328685ed82edd651ab2025-01-08T05:31:31ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042024-12-012012e101150210.1371/journal.pgen.1011502Functional investigation suggests CNTNAP5 involvement in glaucomatous neurodegeneration obtained from a GWAS in primary angle closure glaucoma.Sudipta ChakrabortyJyotishman SarmaShantanu Saha RoySukanya MitraSayani BagchiSankhadip DasSreemoyee SahaSurajit MahapatraSamsiddhi BhattacharjeeMahua MaulikMoulinath AcharyaPrimary angle closure glaucoma (PACG) affects more than 20 million people worldwide, with an increased prevalence in south-east Asia. In a prior haplotype-based Genome Wide Association Study (GWAS), we identified a novel CNTNAP5 genic region, significantly associated with PACG. In the current study, we have extended our perception of CNTNAP5 involvement in glaucomatous neurodegeneration in a zebrafish model, through investigating phenotypic consequences pertinent to retinal degeneration upon knockdown of cntnap5 by translation-blocking morpholinos. While cntnap5 knockdown was successfully validated using an antibody, immunofluorescence followed by western blot analyses in cntnap5-morphant (MO) zebrafish revealed increased expression of acetylated tubulin indicative of perturbed cytoarchitecture of retinal layers. Moreover, significant loss of Nissl substance is observed in the neuro-retinal layers of cntnap5-MO zebrafish eye, indicating neurodegeneration. Additionally, in spontaneous movement behavioural analysis, cntnap5-MO zebrafish have a significantly lower average distance traversed in light phase compared to mismatch-controls, whereas no significant difference was observed in the dark phase, corroborating with vision loss in the cntnap5-MO zebrafish. This study provides the first direct functional evidence of a putative role of CNTNAP5 in visual neurodegeneration.https://doi.org/10.1371/journal.pgen.1011502 |
| spellingShingle | Sudipta Chakraborty Jyotishman Sarma Shantanu Saha Roy Sukanya Mitra Sayani Bagchi Sankhadip Das Sreemoyee Saha Surajit Mahapatra Samsiddhi Bhattacharjee Mahua Maulik Moulinath Acharya Functional investigation suggests CNTNAP5 involvement in glaucomatous neurodegeneration obtained from a GWAS in primary angle closure glaucoma. PLoS Genetics |
| title | Functional investigation suggests CNTNAP5 involvement in glaucomatous neurodegeneration obtained from a GWAS in primary angle closure glaucoma. |
| title_full | Functional investigation suggests CNTNAP5 involvement in glaucomatous neurodegeneration obtained from a GWAS in primary angle closure glaucoma. |
| title_fullStr | Functional investigation suggests CNTNAP5 involvement in glaucomatous neurodegeneration obtained from a GWAS in primary angle closure glaucoma. |
| title_full_unstemmed | Functional investigation suggests CNTNAP5 involvement in glaucomatous neurodegeneration obtained from a GWAS in primary angle closure glaucoma. |
| title_short | Functional investigation suggests CNTNAP5 involvement in glaucomatous neurodegeneration obtained from a GWAS in primary angle closure glaucoma. |
| title_sort | functional investigation suggests cntnap5 involvement in glaucomatous neurodegeneration obtained from a gwas in primary angle closure glaucoma |
| url | https://doi.org/10.1371/journal.pgen.1011502 |
| work_keys_str_mv | AT sudiptachakraborty functionalinvestigationsuggestscntnap5involvementinglaucomatousneurodegenerationobtainedfromagwasinprimaryangleclosureglaucoma AT jyotishmansarma functionalinvestigationsuggestscntnap5involvementinglaucomatousneurodegenerationobtainedfromagwasinprimaryangleclosureglaucoma AT shantanusaharoy functionalinvestigationsuggestscntnap5involvementinglaucomatousneurodegenerationobtainedfromagwasinprimaryangleclosureglaucoma AT sukanyamitra functionalinvestigationsuggestscntnap5involvementinglaucomatousneurodegenerationobtainedfromagwasinprimaryangleclosureglaucoma AT sayanibagchi functionalinvestigationsuggestscntnap5involvementinglaucomatousneurodegenerationobtainedfromagwasinprimaryangleclosureglaucoma AT sankhadipdas functionalinvestigationsuggestscntnap5involvementinglaucomatousneurodegenerationobtainedfromagwasinprimaryangleclosureglaucoma AT sreemoyeesaha functionalinvestigationsuggestscntnap5involvementinglaucomatousneurodegenerationobtainedfromagwasinprimaryangleclosureglaucoma AT surajitmahapatra functionalinvestigationsuggestscntnap5involvementinglaucomatousneurodegenerationobtainedfromagwasinprimaryangleclosureglaucoma AT samsiddhibhattacharjee functionalinvestigationsuggestscntnap5involvementinglaucomatousneurodegenerationobtainedfromagwasinprimaryangleclosureglaucoma AT mahuamaulik functionalinvestigationsuggestscntnap5involvementinglaucomatousneurodegenerationobtainedfromagwasinprimaryangleclosureglaucoma AT moulinathacharya functionalinvestigationsuggestscntnap5involvementinglaucomatousneurodegenerationobtainedfromagwasinprimaryangleclosureglaucoma |